Oral and oropharyngeal squamous cell carcinomas (OSCC) account for nearly 8,000 deaths a year nationally, with South Carolina ranking the highest of the fifty states in oral cancer mortality. Significantly, the survival rate of 51% has not changed over the past thirty years. Because the mortality of OSCC directly relates to the stage of diagnosis, early detection techniques and targeted therapy are clearly needed for enhanced survival rates. A strong correlation exists between the IGF system and cancer; individuals with the highest serum levels of insulin-like growth factor-1 (IGF-1) have the highest incidence of prostate and breast cancer. IGF-1 and IGF-2 mediate their tumorigenic effects through activation of the IGF-1 receptor (IGF-1R). The IGFs also bind with high affinity to a family of soluble proteins known as the IGF binding proteins (IGFBPs), which reduce the bioavailability of the IGFs by sequestering them from the IGF-1R. The IGFBPs are natural inhibitors of the IGF system. As such, they are presently the only known IGF antagonists. Preliminary data suggest that the IGF system may be a target for therapeutics and prevention of OSCC. Our working hypothesis is that the amplification of the IGF system causing the overexpression of IGF-1R, IGF-1 or IGF-2, plays a central role in the molecular pathogenesis of OSCC. To test our hypothesis the following Specific Aims have been formulated: Specific Aim 1: Examine the expression of the IGF system components in model OSCC cell lines and human OSCC tissue, and Specific Aim 2: Determine the role of the C-terminus of lGFBP-2 in IGF binding. [unreadable] [unreadable]